Jan 28, 2025

MedCity News RNAi Biotech Atalanta Unveils $97M to Reach the Clinic in Two Rare Neuro Diseases The structure of Atalanta Therapeutics’ RNA interference drugs enables them to distribute broadly and deeply into brain tissue. Lead programs for Huntington’s disease and a rare inherited form epilepsy are on track to enter the clinic this year. By Frank Vinluan on January 28, 2025 Share Copy LinkCopy Link Using RNA to interfere with a gene’s expression of disease-causing proteins is a validated therapeutic approach, but so far, the products in this drug class only address liver proteins. Reducing levels of certain proteins in the central nervous system could offer a new way to treat neurological disorders. The challenge facing drug developers is getting these therapies deep into the brain. Atalanta Therapeutics has technology that delivers RNA interference therapies into the CNS. The startup has spent the past four years quietly working on its technology and potential drugs. On Tuesday, Atalanta revealed two lead programs for rare neurological disorders that currently have no FDA-approved therapies. The Boston-based startup also announced $97 million in financing to advance those programs to the clinic and support other CNS therapies in its pipeline. An RNA interference (RNAi) therapy uses small pieces of non-coding RNA to block how certain genes are expressed. In 2018, Alnylam Pharmaceuticals’ Onpattro became the first FDA-approved RNAi drug . This therapy is delivered inside a lipid nanoparticle, which preferentially goes to liver cells. Alnylam and others have been pursuing ways to bring RNAi to the CNS. Atalanta, named for the mythical Greek huntress, makes its therapies with oligonucleotides, short pieces of synthetic RNA. Early efforts in oligo and RNAi drugs could not get beyond the outer layer of the brain, Atalanta CEO Alicia Secor said. One of Atalanta’s founders is Craig Mello, a professor in the RNA Therapeutics Institute at the University of Massachusetts Medical School who was awarded the 2006 Nobel Prize in Physiology or Medicine for his RNAi discoveries. Mello’s research includes ways to deliver oligo therapies into the brain. Atalanta does not use lipid nanoparticles or other delivery technologies, Secor said. Instead, the startup’s drugs employ what she described as a divalent structure in which two small-interfering RNA (siRNA) duplexes are joined by a linker. This structure enable the therapy get into the CNS and it imbues the therapy with properties such as potency and durability. “These molecules are very special and have demonstrated the ability to achieve really broad brain distribution in all regions, [and] importantly, deep brain penetration,” Secor said. Mello was particularly interested in developing therapies for Huntington’s disease, a rare neurological disorder that originates deep in the brain. UMass research published in Nature Biotechnology in 2019 described mouse and monkey studies that showed a single injection of divalent siRNA led to silencing of the gene that causes Huntington’s. This silencing lasted at least six months. Soon after the research was published, F-Prime Capital licensed the UMass technology and formed Atalanta with Secor as its first employee. When the startup emerged from stealth in 2021 with $110 million in Series A financing , it also revealed R&D alliances with Biogen and Genentech. Secor acknowledged that it’s unusual for a startup to land two big pharma partnerships at such an early stage, but she said the deals speak to the industry interest in bringing RNAi to the brain. The alliances provided Atalanta with non-dilutive capital that enabled the company to embark on additional preclinical research that further de-risked its technology platform, Secor said. CNS targets of the Genentech partnership remain undisclosed. Huntington’s was part of the Biogen alliance, but Secor said that agreement is unwinding “for business reasons.” Atalanta now has full control of the Huntington’s programs, one of which the startup aims to advance to human testing later this year. Other companies are further along in development with Huntington’s drug candidates. Last month, Novartis agreed to pay $1 billion for rights to a PTC Therapeutics small molecule on track for pivotal testing . Roche and Ionis Pharmaceuticals are partners in the development of tominersen, an antisense oligonucleotide (ASO) that has weathered clinical trial setbacks . Secor describes Atalanta’s technology as a more efficient way of selectively delivering a potent Huntington’s therapy into the brain. “There is no other oligonucleotide that has been able to achieve what we have in terms of knockdown and durability,” Secor said. “I think most people would argue ASO chemistry is good, but RNAi is the next generation.” The other Atalanta program on track to the clinic is a potential treatment for a rare form of epilepsy driven by gain-of-function variants in the KCNT1 gene. Patients who have this disease can experience 50 to 100 seizures daily that aren’t treatable with existing anti-seizure drugs, Secor said. Atalanta’s therapy is designed to reduce levels of KCNT1 protein. In mouse studies, a 50% reduction in protein led to a 70% reduction in seizures, Secor said. Evaluating safety is the main goal of the planned Phase 1 test of the KCNT1 therapy, but this study will also enable Atalanta to quickly demonstrate its technology can work in humans. That’s because seizure activity can also be measured. Reducing seizures in the trial will provide some clinical proof of concept for the drug, and for Atalanta’s technology, Secor said. Atalanta’s latest financing is a Series B round co-led by EQT Life Sciences and Sanofi Ventures. Other participants include new investors RiverVest Venture Partners, Novartis Venture Fund, funds managed by abrdn Inc, Pictet Alternative Advisors, Mirae Asset Financial Group, and GHR Foundation alongside earlier investor F-Prime Capital. Besides the Huntington’s and KCNT1 programs, the Atalanta pipeline currently spans Alzheimer’s disease, pain, and unspecified CNS disorders driven by multiple undisclosed targets. Atalanta is not actively looking for more partners right now, but Secor is leaving the door open. “We’ve got a pretty powerful platform that can basically knock down any transcript in the brain where there’s genetic validation that it’s disease causing,” she said. “There’s a whole universe of targets and we are open to inbound interest. Right now, we’re focused on filing our [investigational new drug applications]. But you know, we might be open [to partnerships] in 2025.” Image by Atalanta Therapeutics